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March 21, 2012

Marijuana and its CD4 Receptors: A New HIV Treatment Strategy?

by Tim Horn

Drugs that target one of the two cellular receptors stimulated by the active ingredient in marijuana may prove to be effective at blocking a form of HIV that has been linked to faster disease progression during late stages of the infection. Though the PLoS One research report highlighting these findings—published March 20 by a team of scientists at Mt. Sinai School of Medicine in New York—stops short of concluding that marijuana is one of nature’s best antiretrovirals, the authors suggest that further study of cannabinoids is needed to ultimately discover drugs with both antiviral and symptom-reducing properties.

Marijuana—purchased legally or illegally and either smoked or ingested—along with its synthetic counterpart Marinol (dronabinol) are used by many people living with HIV to manage various symptoms of illness, including pain, depression and weight loss.

The numerous effects of marijuana are the result of chemical interactions between the drug’s active ingredient, tetrahydrocannabinol (THC), and two receptors on a variety of cells in the body: cannabinoid receptor 1 (CR1) and cannabinoid receptor 2 (CR2).

CR1 receptors are densely populated in the brain and, when stimulated by chemicals like THC, can have a variety of neurological effects. It is THC’s interaction with CR1 in the brain and central nervous system that contributes to marijuana’s “high”-like effects.

THC also interacts with CR2, which is not only found on some cells in the brain, but also on cells of the immune system, gastrointestinal tract and peripheral nervous system. It is THC’s stimulation of CR2 in the latter two compartments that may account for the drug’s positive therapeutic effects on nausea and neuropathic pain, to name a few important symptoms.

CR2 has also been found on a variety of immune system cells and is present on CD4 cells in abundance. While some studies have classified CR2 as a suppressor of CD4 cells and early trials indicated that marijuana use was associated with progression to AIDS, more recent analyses suggest that the drug isn’t associated with significant immune suppression. In fact, both smoked marijuana and Marinol have been associated with increases in CD4 cell counts—along with a decrease in viral load—in at least one short-term study and laboratory experiments.

In effect, the mechanisms by which the interactions between THC and the cannabinoid receptors alter CD4 cell function remain unclear. One particular area of interest, though, is the connection between CR2 and CXCR4, another receptor on immune system cells. For example, CR2 activation blocks CXCR4 from directing the movement of certain cells in the body (chemotaxis). CR2 also plays a role in moving white blood cells out of bone marrow (egress), a role previously attributed largely to CXCR4.

The apparent “cross talk” between CR2 and CXCR4, therefore, led the Mt. Sinai researchers—under the direction of Cristina Maria Costantino, PhD—to explore whether stimulation of CR2 can block the way CXCR4 interacts with a particular form of HIV: CXCR4-tropic virus.

During the early years of untreated HIV infection, HIV primarily targets—or is tropic for—cells with the CCR5 receptor. As HIV disease progresses, however, approximately 50 percent of people living with HIV see their virus develop preference for the CXCR4 receptor on CD4 cells. This particular form of the virus, research has shown, is associated with rapid disease progression, though it is unclear if the emergence of CXCR4-tropic virus is a cause or an effect of immune suppression.

Costantino’s test tube experiments proved encouraging. Using a cannabinoid receptor agonist—a THC-like compound—her team found that activation of CR2 inhibited CXCR4-tropic HIV infection. It did this, not by altering the number of CXCR4 receptors on CD4 cells—this is a therapeutic approach being explored by others—but rather by blocking the receptor’s “signaling process” and interaction with HIV.

According to the PLoS One report, activation of CR2 blocked the ability of CXCR4-tropic virus to infect other cells by 30 to 60 percent. “This inhibition is pronounced in resting cells,” the researchers explain, “which are a target of CXCR4-tropic HIV.”

“Developing a drug that triggers only [CR2] as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading,” said Dr. Costantino in an accompanying news announcement.

As a result of this discovery, additional research at Mt. Sinai is being planned. Specifically, researchers there will be developing a mouse model of late-stage HIV infection in order to test the efficacy of a drug that triggers CR2, not in test tubes, but in living organisms.

(Note: The POZ team reviews all comments before they are posted. Please do not include either ":" or "@" in your comment. The opinions expressed by people providing comments are theirs alone. They do not necessarily reflect the opinions of Smart + Strong, which is not responsible for the accuracy of any of the information supplied by people providing comments.)

Manny Simonelly, Springfield, 2012-07-26 00:18:32
My boyfriend smoked it all the time while he was sick and yet died of AIDS.

brlazarus, Baton Rouge, 2012-06-29 11:25:41
Ken, you have a right to your religious beliefs, but I find it kind of disingenuous to wait for a man-made deity to suddenly bestow a cure. With that logic, this god would have been responsible for the disease. Would a compassionate god create a deadly disease, let millions of people suffer and die, all the while with the cure in his/her back pocket, just waiting to one day say, "Okay, silly humans, you've suffered enough with this one. Here ya go with the cure. Sorry you lost all your friends."

mark, , 2012-06-27 02:03:01
tim,after reading a comment like yours,it makes it hard for one to believe that you were ever on antiretrovirals in your life.quit commenting on a drug your newly infected,if even infected at all butt has ever needed!

woody, South Lake Tahoe, 2012-06-09 19:43:38
28 yrs. HIV+, 15 yrs. no symptoms due to heavy marijuana use. 13 years ago I finally got Toxo, still smoking, feel great but the toxo left me with hemispherical paralysis. In Ca. it is very easy to obtain our medicine now, thank god!

Jimmy, New Orleans Metro, 2012-06-04 12:55:39
I have smoked most of my life. I had a successful career and a stable relationship over 24 years. I would like to think that my decision to continue after becoming poz was a good one. Having said that, I am still on the same meds from the days that protease inhibitors were first introduced and my CD4 and v/l have always remained 1,000 and under 50 copies. This is good news. I don't recommend it to anyone else, all I can say is that it hasn't caused me any adverse problems. 18 years or so.

Ken, Burkinafaso, 2012-04-26 22:02:35
I am glad we are coming very close to the cure but advice we should all wait until they come up or declare marijuana the cure.
We all know the side effects of marijuana smoking, lets us not encourage the youths with this and again lets keep praying that God will send us the real cure in due time.

Keith, EU, 2012-04-26 14:34:58
How much is medical weeb is the US
It has to be cheaper than HAART
The Government in the US and others dont want medical weeb to be seen as helpful or good for you for any illness.
We need to legalize it now
My desire to legalise it has nothing to do with HIV just a general desire.

angerga tarlumun, makurdi, 2012-04-18 08:02:14
we might have noticed since that people who abused cannabis progress less to terminal aids diseases or have we not been very observant?

Aries07, S.W. Missouri, 2012-04-16 16:23:13
I have evidenced marijuana smoking elevating my t-cell counts over a period of 3yrs (secretly from my doctor) and currently cannot smoke it in S.W. Missouri as I will lose my services at our clinic if it is ever found in my blood again! ... Go figure?

True Believer in Pot Therapy !, , 2012-04-12 11:22:34
I've been smoking pot for years. I've been HIV+ for 26 years. I'm lucky and have never developed any opportunistic infections or any other problems. I've wondered why I have been so lucky. These new studies tell me the answer. Smoking Pot has saved me. I swear by it and advise everyone to give it a try. It helps in so many ways and it is not a gateway drug, and I don't seek to hide from reality, I want to live as long as I can; and have a life beyond that of being HIV+.

Alex, Rome, 2012-04-11 09:41:51
I have panick attacks and anxiety if I smoke hash or weed ... for all you guys seems working great ..

burn, birmingham, 2012-04-10 08:59:16
I think it comes down to the fact that we rarely find ourselves with a treatment that suggest few undesirable side effects, let alone mood elevator benefits... dope remains illegal in my country and I only smoked it growing up. Great if they find it as a part of a possible treatment or cure for this illness. It is best kept, i feel, for those with onset of aids as a pain and mood manager.

Robin, new york, 2012-04-10 08:51:07
I have been hiv+ for 21 yrs.my husband died 12yrs ago with the virus.i started meds 3yrs ago because i was going on hep c meds again.we were worried my t cells would go down again.i didnt get rid of the hep c.but my hiv is more than under control.t-cell 719VL undetectable.my daughter and i joke that its the weed thats keeping me healthy.i smoke everyday.never thought it was helping.but who knows.ill keep on smokeing and hopefully ill be around for another 20 yrs.